Research progress on biomarkers of post-traumatic stress disorder

doi:10.3877/cma.j.issn.2095-9141.2025.03.008

Abstract

Abstract:

Post-traumatic stress disorder (PTSD) is a mental health condition that arises following an individual's exposure to traumatic events, often triggered by external factors such as explosions or shock, particularly evident in military conflicts, where its prevalence is significantly high, causing severe repercussions for both patients and society. Currently, the diagnosis of PTSD lacks objective standards, making screening and qualitative assessment challenging. This paper summarizes the latest research progress on genetic susceptibility biomarkers related to PTSD, biomarkers associated with structural and functional changes in the brain as revealed by neuroimaging findings, alterations in peripheral autonomic nervous system function, and specific peripheral fluid biomarkers, while also exploring the potential clinical applications of these biomarkers. The aim of this review is to provide a scientific basis for the early recognition, diagnosis, and personalized treatment of PTSD, thereby promoting the application of biomarkers in clinical practice.

Key words: Post-traumatic stress disorder, Biomarkers, Proteomics, Genetic susceptibility, Magnetic resonance

Zehan Zhang, Xiaowei Fei, Weihao Lyu, Min Cai, Zhuo Zhuang, Huaning Wang, Zhou Fei. Research progress on biomarkers of post-traumatic stress disorder[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2025, 11(03): 185-191.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhsjcswkdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-9141.2025.03.008

https://zhsjcswkdzzz.cma-cmc.com.cn/EN/Y2025/V11/I03/185

References 75

[1]	Su YJ. PTSD and depression in adult burn patients three months postburn: the contribution of psychosocial factors[J]. Gen Hosp Psychiatry, 2023, 82: 33-40. DOI: 10.1016/j.genhosppsych.2023.03.004.
[2]	Maercker A, Cloitre M, Bachem R, et al. Complex post-traumatic stress disorder[J]. Lancet, 2022, 400(10345): 60-72. DOI: 10.1016/S0140-6736(22)00821-2.
[3]	Nanavati HD, Arevalo A, Memon AA, et al. Associations between posttraumatic stress and stroke: a systematic review and meta-analysis[J]. J Trauma Stress, 2023, 36(2): 259-271. DOI: 10.1002/jts.22925.
[4]	van den Berk Clark C, Kansara V, Fedorova M, et al. How does PTSD treatment affect cardiovascular, diabetes and metabolic disease risk factors and outcomes? A systematic review[J]. J Psychosom Res, 2022, 157: 110793. DOI: 10.1016/j.jpsychores.2022.110793.
[5]	Davis LL, Schein J, Cloutier M, et al. The economic burden of posttraumatic stress disorder in the United States from a societal perspective[J]. J Clin Psychiatry, 2022, 83(3): 21m14134. DOI: 10.4088/JCP.21m14134.
[6]	Hansen M, Armour C, McGlinchey E, et al. Investigating the DSM-5 and the ICD-11 PTSD symptoms using network analysis across two distinct samples[J]. Psychol Trauma, 2023, 15(5): 757-766. DOI: 10.1037/tra0001281.
[7]	Merians AN, Spiller T, Harpaz-Rotem I, et al. Post-traumatic stress disorder[J]. Med Clin North Am, 2023, 107(1): 85-99. DOI: 10.1016/j.mcna.2022.04.003.
[8]	Lonnen E, Paskell R. Gender, sex and complex PTSD clinical presentation: a systematic review[J]. Eur J Psychotraumatol, 2024, 15(1): 2320994. DOI: 10.1080/20008066.2024.2320994.
[9]	Petereit-Haack G, Bolm-Audorff U, Romero Starke K, et al. Occupational risk for post-traumatic stress disorder and trauma-related depression: a systematic review with meta-analysis[J]. Int J Environ Res Public Health, 2020, 17(24): 9369. DOI: 10.3390/ijerph17249369.
[10]	Burback L, Brémault-Phillips S, Nijdam MJ, et al. Treatment of posttraumatic stress disorder: a state-of-the-art review[J]. Curr Neuropharmacol, 2024, 22(4): 557-635. DOI: 10.2174/1570159X21666230428091433.
[11]	Diamond PR, Airdrie JN, Hiller R, et al. Change in prevalence of post-traumatic stress disorder in the two years following trauma: a meta-analytic study[J]. Eur J Psychotraumatol, 2022, 13(1): 2066456. DOI: 10.1080/20008198.2022.2066456.
[12]	Koenen KC, Ratanatharathorn A, Ng L, et al. Posttraumatic stress disorder in the World Mental Health Surveys[J]. Psychol Med, 2017, 47(13): 2260-2274. DOI: DOI:10.1017/S0033291717000708.
[13]	Johnson RJ, Antonaccio O, Botchkovar E, et al. War trauma and PTSD in Ukraine's civilian population: comparing urban-dwelling to internally displaced persons[J]. Soc Psychiatry Psychiatr Epidemiol, 2022, 57(9): 1807-1816. DOI: 10.1007/s00127-021-02176-9.
[14]	Ben-Ezra M, Goodwin R, Leshem E, et al. PTSD symptoms among civilians being displaced inside and outside the Ukraine during the 2022 Russian invasion[J]. Psychiatry Res, 2023, 320: 115011. DOI: 10.1016/j.psychres.2022.115011.
[15]	Karatzias T, Shevlin M, Ben-Ezra M, et al. War exposure, posttraumatic stress disorder, and complex posttraumatic stress disorder among parents living in Ukraine during the Russian war[J]. Acta Psychiatr Scand, 2023, 147(3): 276-285. DOI: 10.1111/acps.13529.
[16]	Skórzewska A, Lehner M, Wisłowska-Stanek A, et al. Individual susceptibility or resistance to posttraumatic stress disorder-like behaviours[J]. Behav Brain Res, 2020, 386: 112591. DOI: 10.1016/j.bbr.2020.112591.
[17]	James LM, Georgopoulos AP. Immunogenetics of posttraumatic stress disorder (PTSD) in women veterans[J]. Brain Behav Immun Health, 2022, 26: 100567. DOI: 10.1016/j.bbih.2022.100567.
[18]	Vaccarino V, Shah AJ, Moncayo V, et al. Posttraumatic stress disorder, myocardial perfusion, and myocardial blood flow: a longitudinal twin study[J]. Biol Psychiatry, 2022, 91(7): 615-625. DOI: 10.1016/j.biopsych.2021.09.016.
[19]	Cusack SE, Maihofer AX, Bustamante D, et al. Genetic influences on testosterone and PTSD[J]. J Psychiatr Res, 2024, 174: 8-11. DOI: 10.1016/j.jpsychires.2024.04.002.
[20]	Tseilikman VE, Tseilikman OB, Pashkov AA, et al. Mechanisms of susceptibility and resilience to PTSD: role of dopamine metabolism and BDNF expression in the hippocampus[J]. Int J Mol Sci, 2022, 23(23): 14575. DOI: 10.3390/ijms232314575.
[21]	Le Tran N, Wang Y, Nie G. Podocalyxin in normal tissue and epithelial cancer[J]. Cancers (Basel), 2021, 13(12): 2863. DOI: 10.3390/cancers13122863.
[22]	Mehlig K, Foraita R, Nagrani R, et al. Genetic associations vary across the spectrum of fasting serum insulin: results from the European IDEFICS/I. Family children's cohort[J]. Diabetologia, 2023, 66(10): 1914-1924. DOI: 10.1007/s00125-023-05957-w.
[23]	Sanders SS, Hernandez LM, Soh H, et al. The palmitoyl acyltransferase ZDHHC14 controls Kv1-family potassium channel clustering at the axon initial segment[J]. Elife, 2020, 9: e56058. DOI: 10.7554/eLife.56058.
[24]	Nievergelt CM, Maihofer AX, Klengel T, et al. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci[J]. Nat Commun, 2019, 10(1): 4558. DOI: 10.1038/s41467-019-12576-w.
[25]	Parthasarathy R, Santiago F, McCluskey P, et al. The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies[J]. Trends Microbiol, 2023, 31(2): 142-158. DOI: 10.1016/j.tim.2022.08.008.
[26]	Zhang X, Han Y, Liu X, et al. Assessment of genetic variants in D2 dopamine receptor (DRD2) gene as risk factors for post-traumatic stress disorder (PTSD) and major depressive disorder (MDD): a systematic review and meta-analysis[J]. J Affect Disord, 2023, 328: 312-323. DOI: 10.1016/j.jad.2023.02.001.
[27]	Polimanti R, Wendt FR. Posttraumatic stress disorder: from gene discovery to disease biology[J]. Psychol Med, 2021, 51(13): 2178-2188. DOI: 10.1017/S0033291721000210.
[28]	Stein MB, Levey DF, Cheng Z, et al. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program[J]. Nat Genet, 2021, 53(2): 174-184. DOI: 10.1038/s41588-020-00767-x.
[29]	Del Casale A, Ferracuti S, Barbetti AS, et al. Grey matter volume reductions of the left hippocampus and amygdala in PTSD: a coordinate-based meta-analysis of magnetic resonance imaging studies[J]. Neuropsychobiology, 2022, 81(4): 257-264. DOI: 10.1159/000522003.
[30]	Chen LW, Sun D, Davis SL, et al. Smaller hippocampal CA1 subfield volume in posttraumatic stress disorder[J]. Depress Anxiety, 2018, 35(11): 1018-1029. DOI: 10.1002/da.22833.
[31]	Morey RA, Clarke EK, Haswell CC, et al. Amygdala nuclei volume and shape in military veterans with posttraumatic stress disorder[J]. Biol Psychiatry Cogn Neurosci Neuroimaging, 2020, 5(3): 281-290. DOI: 10.1016/j.bpsc.2019.11.016.
[32]	Szeszko PR, Bierer LM, Bader HN, et al. Cingulate and hippocampal subregion abnormalities in combat-exposed veterans with PTSD[J]. J Affect Disord, 2022, 311: 432-439. DOI: 10.1016/j.jad.2022.05.081.
[33]	Kredlow MA, Fenster RJ, Laurent ES, et al. Prefrontal cortex, amygdala, and threat processing: implications for PTSD[J]. Neuropsychopharmacology, 2022, 47(1): 247-259. DOI: 10.1038/s41386-021-01155-7.
[34]	Hinojosa CA, George GC, Ben-Zion Z. Neuroimaging of posttraumatic stress disorder in adults and youth: progress over the last decade on three leading questions of the field[J]. Mol Psychiatry, 2024, 29(10): 3223-3244. DOI: 10.1038/s41380-024-02558-w.
[35]	Wang X, Xie H, Chen T, et al. Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis[J]. Mol Psychiatry, 2021, 26(8): 4331-4343. DOI: 10.1038/s41380-020-00967-1.
[36]	Logue MW, van Rooij SJH, Dennis EL, et al. Smaller hippocampal volume in posttraumatic stress disorder: a multisite ENIGMA-PGC study: subcortical volumetry results from posttraumatic stress disorder consortia[J]. Biol Psychiatry, 2018, 83(3): 244-253. DOI: 10.1016/j.biopsych.2017.09.006.
[37]	Dennis EL, Disner SG, Fani N, et al. Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium [J]. Mol Psychiatry, 2021, 26(8): 4315-4330. DOI: 10.1038/s41380-019-0631-x.
[38]	Akiki TJ, Averill CL, Wrocklage KM, et al. The association of PTSD symptom severity with localized hippocampus and amygdala abnormalities[J]. Chronic Stress (Thousand Oaks), 2017, 1: 2470547017724069. DOI: 10.1177/2470547017724069.
[39]	Misaki M, Phillips R, Zotev V, et al. Real-time fMRI amygdala neurofeedback positive emotional training normalized resting-state functional connectivity in combat veterans with and without PTSD: a connectome-wide investigation[J]. Neuroimage Clin, 2018, 20: 543-555. DOI: 10.1016/j.nicl.2018.08.025.
[40]	Haris EM, Bryant RA, Williamson T, et al. Functional connectivity of amygdala subnuclei in PTSD: a narrative review[J]. Mol Psychiatry, 2023, 28(9): 3581-3594. DOI: 10.1038/s41380-023-02291-w.
[41]	Nicholson AA, Rabellino D, Densmore M, et al. Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: a preliminary analysis[J]. Hum Brain Mapp, 2018, 39(11): 4258-4275. DOI: 10.1002/hbm.24244.
[42]	Misaki M, Phillips R, Zotev V, et al. Brain activity mediators of PTSD symptom reduction during real-time fMRI amygdala neurofeedback emotional training[J]. Neuroimage Clin, 2019, 24: 102047. DOI: 10.1016/j.nicl.2019.102047.
[43]	Dossi G, Delvecchio G, Prunas C, et al. Neural bases of cognitive impairments in post-traumatic stress disorders: a mini-review of functional magnetic resonance imaging findings[J]. Front Psychiatry, 2020, 11: 176. DOI: 10.3389/fpsyt.2020.00176.
[44]	Jagger-Rickels A, Stumps A, Rothlein D, et al. Impaired executive function exacerbates neural markers of posttraumatic stress disorder[J]. Psychol Med, 2021, 1-14. DOI: 10.1017/s0033291721000842.
[45]	Akiki TJ, Averill CL, Abdallah CG. A network-based neurobiological model of PTSD: evidence from structural and functional neuroimaging studies[J]. Curr Psychiatry Rep, 2017, 19(11): 81. DOI: 10.1007/s11920-017-0840-4.
[46]	Keefe JR, Suarez-Jimenez B, Zhu X, et al. Elucidating behavioral and functional connectivity markers of aberrant threat discrimination in PTSD[J]. Depress Anxiety, 2022, 39(12): 891-901. DOI: 10.1002/da.23295.
[47]	Crozier JC, Wang L, Huettel SA, et al. Neural correlates of cognitive and affective processing in maltreated youth with posttraumatic stress symptoms: does gender matter?[J] Dev Psychopathol, 2014, 26(2): 491-513. DOI: 10.1017/S095457941400016X.
[48]	Suo X, Zuo C, Lan H, et al. Multilayer network analysis of dynamic network reconfiguration in adults with posttraumatic stress disorder[J]. Biol Psychiatry Cogn Neurosci Neuroimaging, 2023, 8(4): 452-461. DOI: 10.1016/j.bpsc.2022.09.003.
[49]	Beutler S, Mertens YL, Ladner L, et al. Trauma-related dissociation and the autonomic nervous system: a systematic literature review of psychophysiological correlates of dissociative experiencing in PTSD patients[J]. Eur J Psychotraumatol, 2022, 13(2): 2132599. DOI: 10.1080/20008066.2022.2132599.
[50]	Campbell AA, Wisco BE, Silvia PJ, et al. Resting respiratory sinus arrhythmia and posttraumatic stress disorder: a meta-analysis[J]. Biol Psychol, 2019, 144: 125-135. DOI: 10.1016/j.biopsycho.2019.02.005.
[51]	Campbell AA, Wisco BE. Respiratory sinus arrhythmia reactivity in anxiety and posttraumatic stress disorder: a review of literature[J]. Clin Psychol Rev, 2021, 87: 102034. DOI: 10.1016/j.cpr.2021.102034.
[52]	Schneider M, Schwerdtfeger A. Autonomic dysfunction in posttraumatic stress disorder indexed by heart rate variability: a meta-analysis[J]. Psychol Med, 2020, 50(12): 1937-1948. DOI: 10.1017/S003329172000207X.
[53]	Park JE, Lee JY, Kang SH, et al. Heart rate variability of chronic posttraumatic stress disorder in the Korean veterans[J]. Psychiatry Res, 2017, 255: 72-77. DOI: 10.1016/j.psychres.2017.05.011.
[54]	Wiltshire CN, Kouri N, Wanna CP, et al. Resting heart rate associations with violence exposure and posttraumatic stress symptoms: sex differences in children[J]. Biol Sex Differ, 2024, 15(1): 28. DOI: 10.1186/s13293-024-00606-2.
[55]	Sheikh SA, Shah AJ, Bremner JD, et al. Impedance cardiogram based exploration of cardiac mechanisms in post-traumatic stress disorder during trauma recall[J]. Psychophysiology, 2024, 61(4): e14488. DOI: 10.1111/psyp.14488.
[56]	Lori A, Schultebraucks K, Galatzer-Levy I, et al. Transcriptome-wide association study of post-trauma symptom trajectories identified GRIN3B as a potential biomarker for PTSD development [J]. Neuropsychopharmacology, 2021, 46(10): 1811-1820. DOI: 10.1038/s41386-021-01073-8.
[57]	Chevalier CM, Krampert L, Schreckenbach M, et al. MMP9 mRNA is a potential diagnostic and treatment monitoring marker for PTSD: evidence from mice and humans[J]. Eur Neuropsychopharmacol, 2021, 51: 20-32. DOI: 10.1016/j.euroneuro.2021.04.014.
[58]	Vishnoi A, Rani S. miRNA biogenesis and regulation of diseases: an updated overview[J]. Methods Mol Biol, 2023, 2595: 1-12. DOI: 10.1007/978-1-0716-2823-2_1.
[59]	Diener C, Keller A, Meese E. Emerging concepts of miRNA therapeutics: from cells to clinic[J]. Trends Genet, 2022, 38(6): 613-626. DOI: 10.1016/j.tig.2022.02.006.
[60]	Du X, Lv J, Feng J, et al. Plasma exosomes lncRNA-miRNA-mRNA network construction and its diagnostic efficacy identification in first-episode schizophrenia[J]. BMC Psychiatry, 2023, 23(1): 611. DOI: 10.1186/s12888-023-05052-9.
[61]	Paccosi E, Proietti-De-Santis L. Parkinson's disease: from genetics and epigenetics to treatment, a miRNA-based strategy[J]. Int J Mol Sci, 2023, 24(11): 9547. DOI: 10.3390/ijms24119547.
[62]	Gupta S, Guleria RS, Szabo YZ. MicroRNAs as biomarker and novel therapeutic target for posttraumatic stress disorder in veterans[J]. Psychiatry Res, 2021, 305: 114252. DOI: 10.1016/j.psychres.2021.114252.
[63]	Bam M, Yang X, Zumbrun EE, et al. Decreased AGO2 and DCR1 in PBMCs from war veterans with PTSD leads to diminished miRNA resulting in elevated inflammation[J]. Transl Psychiatry, 2017, 7(8): e1222. DOI: 10.1038/tp.2017.185.
[64]	Martin CG, Kim H, Yun S, et al. Circulating miRNA associated with posttraumatic stress disorder in a cohort of military combat veterans[J]. Psychiatry Res, 2017, 251: 261-265. DOI: 10.1016/j.psychres.2017.01.081
[65]	Rim EY, Clevers H, Nusse R. The Wnt pathway: from signaling mechanisms to synthetic modulators[J]. Annu Rev Biochem, 2022, 91: 571-598. DOI: 10.1146/annurev-biochem-040320-103615.
[66]	Berumen Sánchez G, Bunn KE, Pua HH, et al. Extracellular vesicles: mediators of intercellular communication in tissue injury and disease[J]. Cell Commun Signal, 2021, 19(1): 104. DOI: 10.1186/s12964-021-00787-y.
[67]	Garcia-Martin R, Wang G, Brandão BB, et al. MicroRNA sequence codes for small extracellular vesicle release and cellular retention[J]. Nature, 2022, 601(7893): 446-451. DOI: 10.1038/s41586-021-04234-3.
[68]	Guedes VA, Lai C, Devoto C, et al. Extracellular vesicle proteins and microRNAs are linked to chronic post-traumatic stress disorder symptoms in service members and veterans with mild traumatic brain injury[J]. Front Pharmacol, 2021, 12: 745348. DOI: 10.3389/fphar.2021.745348.
[69]	Lee MY, Baxter D, Scherler K, et al. Distinct profiles of cell-free microRNAs in plasma of veterans with post-traumatic stress disorder[J]. J Clin Med, 2019, 8(7): 963. DOI: 10.3390/jcm8070963.
[70]	Zhang L, Hu XZ, Li X, et al. Potential chemokine biomarkers associated with PTSD onset, risk and resilience as well as stress responses in US military service members[J]. Transl Psychiatry, 2020, 10(1): 31. DOI: 10.1038/s41398-020-0693-1.
[71]	Xu M, Lin Z, Siegel CE, et al. Screening for PTSD and TBI in veterans using routine clinical laboratory blood tests[J]. Transl Psychiatry, 2023, 13(1): 64. DOI: 10.1038/s41398-022-02298-x.
[72]	Meng X, Liu D, Guan Y. Advances in the application of label-free quantitative proteomics techniques in malignancy research[J]. Biomed Chromatogr, 2023, 37(7): e5667. DOI: 10.1002/bmc.5667.
[73]	Muhie S, Gautam A, Yang R, et al. Molecular signatures of post-traumatic stress disorder in war-zone-exposed veteran and active-duty soldiers[J]. Cell Rep Med, 2023, 4(5): 101045. DOI: 10.1016/j.xcrm.2023.101045.
[74]	Kuan PF, Clouston S, Yang X, et al. Molecular linkage between post-traumatic stress disorder and cognitive impairment: a targeted proteomics study of World Trade Center responders[J]. Transl Psychiatry, 2020, 10(1): 269. DOI: 10.1038/s41398-020-00958-4.
[75]	Waszczuk MA, Kuan PF, Yang X, et al. Discovery and replication of blood-based proteomic signature of PTSD in 9/11 responders[J]. Transl Psychiatry, 2023, 13(1): 8. DOI: 10.1038/s41398-022-02302-4.

Please choose a citation manager

Content to export